text: The vanilloid receptor (TRPV1) is one of six sub-members that belong to the transient receptor potential channel (TRP) superfamily. TRPV1 was the first mammalian member to be discovered and is a non-selective cation channel permeable for calcium. The receptor is made of four identical subunits each with six transmembrane segments, S1-S6, with an aqueous pore between the fifth and sixth segments. This region forms the channel conductive pore and contains the N- and C-termini on the cytosolic side of the cell membrane.
  Capsaicin and RTX, elicit burning pain by activating a non-selective cation channel expressed on sensory nerve endings. When capsaicin was found to have analgesic effects in preclinical studies much emphasis was put into the research of the receptor/channel that capsaicin binds to and activates. Besides being activated by capsaicin, TRPV1 also responds to a wide range of exogenous and endogenous chemical ligands as well as physical stimuli such as heat over 42 °C and changes in more diverse activators such as protons (acid, pH<6). TRPV1 is also subject to regulation by changes in membrane potential and this intrinsic voltage-dependence is thought to underlie the gating mechanism of this non-selective cation channel which leads to the influx of sodium and calcium ions. Importantly, TRPV1 activity is also subject to regulation by a host of intracellular signaling cascades such as G-protein coupled receptor signaling, that are implicated in the responses to algogenic agents, inflammatory mediators and injury.